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The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer

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Abstract

Cervical cancer is the leading cause of cancer-related death among women worldwide. Identifying an effective treatment with fewer side effects is imperative, because all of the current treatments have unique disadvantages. Aldo–keto reductase family 1 member B1 (AKR1B1) is highly expressed in various cancers and is associated with tumor development, but has not been studied in cervical cancer. In the current study, we used CRISPR/Cas9 technology to establish a stable HeLa cell line with AKR1B1 knockout. In vitro, AKR1B1 knockout inhibited the proliferation, migration and invasion of HeLa cells, providing evidence that AKR1B1 is an innovative therapeutic target. Notably, the clinically used epalrestat, an inhibitor of aldose reductases, including AKR1B1, had the same effect as AKR1B1 knockout on HeLa cells. This result suggests that epalrestat could be used in the clinical treatment of cervical cancer, a prospect that undoubtedly requires further research. Moreover, aiming to determine the underlying regulatory mechanism of AKR1B1, we screened a series of differentially regulated genes (DEGs) by RNA sequencing and verified selected DEGs by quantitative RT-PCR. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs revealed a correlation between AKR1B1 and cancer. In summary, epalrestat inhibits the progression of cervical cancer by inhibiting AKR1B1, and thus may be a new drug for the clinical treatment of cervical cancer.

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Acknowledgements

This study was supported by grants from the Key Research and Development Plan of Jiangsu Province (No. BE2019692), Postdoctoral Science Foundation of China (Grant No. 2019M661909), the Social Development Foundation of Nantong City (Grant Nos. MS22018006, MS12019018, MS12019020), and Teaching Research Project of Affiliated Hospital of Nantong University (Tfj 18006).

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  1. Jie Ji and Min-Xue Xu contributed equally to this work.

Authors and Affiliations

  1. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Jie Ji, Min-Xue Xu & Ming-Bing Xiao

  2. Department of Gastroenterology and Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, 226001, People’s Republic of China

    Jie Ji, Min-Xue Xu, Feng Jiang, Zhao-Xiu Liu & Ming-Bing Xiao

  3. Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Jie Ji, Min-Xue Xu & Sheng-Ze Zhu

  4. Chinese Medicine 193, First Clinical Medical School, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China

    Tian-Yang Qian

  5. Department of Gastroenterology, Second People’s Hospital of Nantong, Nantong, 226001, Jiangsu, People’s Republic of China

    Wei-Song Xu

  6. Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Juan Zhou

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  1. Jie Ji
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Ji, J., Xu, MX., Qian, TY. et al. The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer. Mol Biol Rep 47, 6091–6103 (2020). https://doi.org/10.1007/s11033-020-05685-z

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